The major aim of this project is to develop new techniques and to improve existing methods in high-resolution, Two-dimensional NMR spectroscopy for applications in studies of the structure and dynamics of biological macromolecules such as protein and nucleic acids. Recently introduced experiments involving coherence transfer via isotropic mixing and magnetization transfer via nuclear Overhauser effects (NOE) in the rotating frame have been shown to have great potential for facilitating resonance assignments and obtaining distance constraints for structural determinations, respectively. However, in practical terms the coherence transfer process in the isotropic mixing experiment has not been well characterized theoretically, nor has the precise behaviour of coherence transfer pathways in the rotating-frame NOE experiment; in the latter experiment artifacts can be obtained which are identical in appearance to valid transverse NOE peaks and which arise through the presence of coherence transfer processes. One goal of this project will be to carry out a thorough, theoretical analysis of these experiments and to optimize them for use in studies of biomolecules. Another goal of this project will be to perform a theoretical investigation of exchange effects in multiple quantum spectroscopy. NMR spectroscopy is a very important tool for examining exchange phenomena, and has been employed extensively in a variety of ways in single quantum experiments. No description of exchange effects in multiple quantum spectroscopy has yet been provided, however. Such effects in multiple quantum spectra can provide unique information about exchanging systems which is not available from single quantum experiments. Heteronuclear, two-dimensional NMR spectroscopy has the potential of supplying a wealth of information in studies of the structure and dynamics of biomolecules. In particular, measurements of the NMR relaxation rates of selected nuclei such as carbon-13 can be used to determine motional correlation times for local fragments within a molecule. Lack of sensitivity is a major problem in measuring such relaxation rates; in the present proposal efforts will be directed towards developing new methods for obtaining relaxation rates of rare nuclei with improved sensitivity. In addition, modified sequences for recording heteronuclear correlation spectra will be investigated in an attempt to improve the suppression of undesirable signals. Over the last five years or so many new 2D NMR techniques have been proposed for use in studying proteins sand nucleic acids. The usefulness of these techniques is largely determined by the amount of information available in the 2D spectra, which in turn is dependent on the quality of such spectra. It is proposed in the present project to examine the possibility of improving the quality of spectra which are obtained with current methodologies by modifying the pulse sequences, acquisition parameters, and data processing procedures.